Effect of Inflammatory Cytokines/Chemokines on Pulmonary Tuberculosis Culture Conversion and Disease Severity in HIV-Infected and -Uninfected Individuals From South Africa
Novel tuberculosis (TB) prevention and control strategies are urgently required. Utilising specimens from the Improving Retreatment Success (NCT02114684) trial we assessed the associations between inflammatory markers, measured during active TB, with treatment response and disease severity in HIV-in...
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Published in | Frontiers in immunology Vol. 12; p. 641065 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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01.04.2021
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Abstract | Novel tuberculosis (TB) prevention and control strategies are urgently required. Utilising specimens from the Improving Retreatment Success (NCT02114684) trial we assessed the associations between inflammatory markers, measured during active TB, with treatment response and disease severity in HIV-infected and uninfected individuals. Multiplex immunoassays and ELISA were used to measure plasma expression of 24 cytokines/chemokines. Cytokines were log transformed to adjust for skewness. We conducted a nested, un-matched, case (n= 31) - control (n=101) study with cases defined as those participants who failed to sputum culture convert within 8-weeks of TB treatment initiation. Additionally, we examined the association between the measured cytokines and time to culture conversion and presence of lung cavitation using cox proportional hazards and logistic regression models, respectively. Multivariable analyses adjusted for a wide range of baseline clinical and demographic variables. IP-10 expression during active TB was associated with increased odds of sputum culture conversion by 8-weeks overall (aOR 4.255, 95% CI 1.025 - 17.544, p=0.046)) and among HIV-infected individuals (OR 10.204, 95% CI 1.247 - 83.333, p=0.030). Increased MCP-3 (aHR 1.723, 95% CI 1.040 - 2.855, p=0.035) and IL-6 (aHR 1.409, 95% CI 1.045 - 1.899, p=0.024) expression was associated with a shorter time to culture conversion in the total cohort. Higher plasma expression of IL-6 (aHR 1.783, 95% CI 1.128 - 2.820, p=0.013), IL-1RA (aHR 2.595, 95% CI 1.136 - 5.926, p=0.024), IP-10 (aHR 2.068, 95% CI 1.034 - 4.137, p=0.040) and IL-1α (aHR 2.008, 95% CI 1.053 - 3.831, p=0.035) were significantly associated with shorter time to culture conversion among HIV-infected individuals. Increased IL-6 and IL-1RA expression was significantly associated with the presence of lung cavitation during active TB in the total cohort (OR 2.543, 95% CI 1.254 - 5.160, p=0.010), (OR 4.639, 95% CI 1.203 - 21.031, p=0.047) and in HIV-infected individuals (OR 2.644, 95% CI 1.062 - 6.585, p=0.037), (OR 7.795, 95% CI 1.177 - 51.611, p=0.033) respectively. Our results indicate that inflammatory cytokines/chemokines play an important role in TB disease outcome. Importantly, the observed associations were stronger in multivariable models highlighting the impact of behavioural and clinical variables on the expression of immune markers as well as their potential effects on TB outcome. |
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AbstractList | Novel tuberculosis (TB) prevention and control strategies are urgently required. Utilising specimens from the Improving Retreatment Success (NCT02114684) trial we assessed the associations between inflammatory markers, measured during active TB, with treatment response and disease severity in HIV-infected and uninfected individuals. Multiplex immunoassays and ELISA were used to measure plasma expression of 24 cytokines/chemokines. Cytokines were log transformed to adjust for skewness. We conducted a nested, un-matched, case (n= 31) - control (n=101) study with cases defined as those participants who failed to sputum culture convert within 8-weeks of TB treatment initiation. Additionally, we examined the association between the measured cytokines and time to culture conversion and presence of lung cavitation using cox proportional hazards and logistic regression models, respectively. Multivariable analyses adjusted for a wide range of baseline clinical and demographic variables. IP-10 expression during active TB was associated with increased odds of sputum culture conversion by 8-weeks overall (aOR 4.255, 95% CI 1.025 – 17.544, p=0.046)) and among HIV-infected individuals (OR 10.204, 95% CI 1.247 – 83.333, p=0.030). Increased MCP-3 (aHR 1.723, 95% CI 1.040 – 2.855, p=0.035) and IL-6 (aHR 1.409, 95% CI 1.045 – 1.899, p=0.024) expression was associated with a shorter time to culture conversion in the total cohort. Higher plasma expression of IL-6 (aHR 1.783, 95% CI 1.128 – 2.820, p=0.013), IL-1RA (aHR 2.595, 95% CI 1.136 – 5.926, p=0.024), IP-10 (aHR 2.068, 95% CI 1.034 – 4.137, p=0.040) and IL-1α (aHR 2.008, 95% CI 1.053 – 3.831, p=0.035) were significantly associated with shorter time to culture conversion among HIV-infected individuals. Increased IL-6 and IL-1RA expression was significantly associated with the presence of lung cavitation during active TB in the total cohort (OR 2.543, 95% CI 1.254 – 5.160, p=0.010), (OR 4.639, 95% CI 1.203 – 21.031, p=0.047) and in HIV-infected individuals (OR 2.644, 95% CI 1.062 – 6.585, p=0.037), (OR 7.795, 95% CI 1.177 – 51.611, p=0.033) respectively. Our results indicate that inflammatory cytokines/chemokines play an important role in TB disease outcome. Importantly, the observed associations were stronger in multivariable models highlighting the impact of behavioural and clinical variables on the expression of immune markers as well as their potential effects on TB outcome. |
Author | Rambaran, Santhuri Lewis, Lara Naidoo, Kogieleum Hassan-Moosa, Razia Padayatchi, Nesri Scriba, Thomas J Sivro, Aida Govender, Dhineshree Samsunder, Natasha |
AuthorAffiliation | 3 Department of Pathology, South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town , Cape Town , South Africa 4 Department of Medical Microbiology, University of KwaZulu-Natal , Durban , South Africa 1 Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban , South Africa 2 MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal , Durban , South Africa |
AuthorAffiliation_xml | – name: 3 Department of Pathology, South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town , Cape Town , South Africa – name: 1 Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban , South Africa – name: 2 MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal , Durban , South Africa – name: 4 Department of Medical Microbiology, University of KwaZulu-Natal , Durban , South Africa |
Author_xml | – sequence: 1 givenname: Santhuri surname: Rambaran fullname: Rambaran, Santhuri organization: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa – sequence: 2 givenname: Kogieleum surname: Naidoo fullname: Naidoo, Kogieleum organization: MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa – sequence: 3 givenname: Lara surname: Lewis fullname: Lewis, Lara organization: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa – sequence: 4 givenname: Razia surname: Hassan-Moosa fullname: Hassan-Moosa, Razia organization: MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa – sequence: 5 givenname: Dhineshree surname: Govender fullname: Govender, Dhineshree organization: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa – sequence: 6 givenname: Natasha surname: Samsunder fullname: Samsunder, Natasha organization: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa – sequence: 7 givenname: Thomas J surname: Scriba fullname: Scriba, Thomas J organization: Department of Pathology, South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa – sequence: 8 givenname: Nesri surname: Padayatchi fullname: Padayatchi, Nesri organization: MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa – sequence: 9 givenname: Aida surname: Sivro fullname: Sivro, Aida organization: Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa |
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Copyright | Copyright © 2021 Rambaran, Naidoo, Lewis, Hassan-Moosa, Govender, Samsunder, Scriba, Padayatchi and Sivro. Copyright © 2021 Rambaran, Naidoo, Lewis, Hassan-Moosa, Govender, Samsunder, Scriba, Padayatchi and Sivro 2021 Rambaran, Naidoo, Lewis, Hassan-Moosa, Govender, Samsunder, Scriba, Padayatchi and Sivro |
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Keywords | Tuberculosis HIV biomarker inflammation lung cavitation |
Language | English |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Hazel Marguerite Dockrell, University of London, United Kingdom This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology Reviewed by: Maeva Dupont, University of Oxford, United Kingdom; Jun-Jun Yeh, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Taiwan; Delia Goletti, Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IRCCS), Italy |
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Title | Effect of Inflammatory Cytokines/Chemokines on Pulmonary Tuberculosis Culture Conversion and Disease Severity in HIV-Infected and -Uninfected Individuals From South Africa |
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